CKemmerer Hepatitis C Market Presentation

Therapeutic Area Analysis: Hepatitis C Protease Inhibitors

Charles Kemmerer

Pharm5472 – Pharmaceutical Marketing

November 2013

Hepatitis C: Disease Background

Sources: Photo – Web MD, A Visual Guide to Hepatitis

1.WHO: www.who.int/mediacentre/factsheets/fs164/en/

2.Forbes: A Public Health and Healthcare Spending Time Bomb: Hepatitis C (6/19/2013)

3.http://www.cdc.gov/hepatitis/hcv/hcvfaq.htm

Hepatitis C: Disease Background (Continued)

• HCV is transmitted via blood-to-blood contact.2 The most common exposures occur via:

– Injection drug use (currently the most common means of HCV transmission in the US)– Receipt of donated blood, blood products, and organs (rare in the US since blood screening

became available in 1992)– Needle stick injuries in health care settings– Birth to an HCV-infected mother3

• The complications of HCV-related disease typically take 20-40 years to develop in an individual once infected2

• Overall, HCV infection reduces life expectancy by 8-12 years and varies by individual2

• There are six distinct HCV Genotypes. Genotype-1 is the most common in the United States. Once a person’s genotype is identified, it does not change during the course of disease3

2. Forbes: A Public Health and Healthcare Spending Time Bomb: Hepatitis C (6/19/2013)

3. http://www.cdc.gov/hepatitis/hcv/hcvfaq.htm

Risk factors

• HCV testing is recommended for anyone at increased risk for HCV infection including:• Persons born from 1945 through 1965• Persons who have ever injected illegal drugs• Recipients of clotting factor concentrates made before 1987 • Recipients of blood transfusions or solid organ transplants before July 1992 • Patients who have ever received long-term hemodialysis treatment• Persons with known exposures to HCV, such as

– Healthcare workers after needle sticks involving HCV-positive blood – Recipients of blood or organs from a donor who later tested HCV-positive

• All persons with HIV infection• Patients with signs or symptoms of liver disease (e.g., abnormal liver enzyme tests) • Children born to HCV-positive mothers (after age 18 months)3

3. http://www.cdc.gov/hepatitis/hcv/hcvfaq.htm

HCV Treatment

• Combination therapy with pegylated interferon and ribavirin is the treatment of choice, resulting in sustained virologic response rates of 40%–80% (up to 50% for patients infected with genotype 1, and up to 80% for patients infected with genotypes 2 or 3)3

• The “gold standard”of treating HCV (pegylated interferon and ribavirin combination) leaves much to be desired and many asymptomatic patients forego treatment because of the poor safety profile, tolerability issues and low success rate.2

• Treatment success rates are now being improved with the addition of polymerase and protease inhibitors to standard pegylated interferon/ribavirin combination therapy3

• In May 2011, Merck’s Victrelis (boceprevir) and Vertex’s Incivek (telaprevir) were approved to treat Genotype-1 HCV, in combination with pegylated interferon and ribavirin 2

• In addition, a handful of new agents are currently in development for the treatment of HCV. These new HCV regimens are expected to capture a significant portion of the HCV market2

2. Forbes: A Public Health and Healthcare Spending Time Bomb: Hepatitis C (6/19/2013)

3. http://www.cdc.gov/hepatitis/hcv/hcvfaq.htm

HCV Market• There are an estimated 130-180 million people infected with

HCV worldwide– Approximately 3-4 million infected in the US– Estimates are that 80,000 are currently being treated– Current Standard of care has two significant “compliance

roadblocks”:• Course of treatment is extremely long (average 48 weeks)• Interferon must be injected

• The HCV market was estimated to be $3.8 billion in 2011• The market is forecasted to grow to $15-18 billion by 2020

Interferon Example- Pegasys- Dosage FormsOnce weekly Injection

HCV Protease Inhibitor US Sales (2012)

Drug Mfg. US Sales (millions)

Victrelis Merck $273.4

Incivek Vertex $1380.5

mmm-online, June 2013

Hepatitis C Market Growth

Estimated growth in Hepatitis C Market Share- By Company

Incivek- telaprevir-Patient Site

Incviek- telaprevir- Indication

Source: Incivek PI (upsi_telaprevir.pdf)

Incivek- Indications- PI

Incivek- telaprevir- “Cocktail Therapy”

Incivek- telaprevir- dosing

Incivek- telaprevir- Dosing-PI

Source: Incivek PI (upsi_telaprevir.pdf)

3 tablets twice a day= 6 tablets per day

Invicek- telaprevir- treatment naïve patients

Incivek- telaprevir- relapsed patients

Incivek- telaprevir- prior treatment

Incivek- telaprevir- prior non-responders

Incivek- telaprevir- financial assistance

Incivek- telaprevir- patient support

Incivek- telaprevir- patient support

Incivek- telapravir- HCP site“click-through” screen

Incivek- telaprevir- HCP site

Incivek- telaprevir- HCP site

Incivek- telaprevir- Clinical Trials

Incivek- telaprevir- Clinical Trials

Incivek- telaprevir- Clinical Trials

Incivek- telaprevir- Clinical Trials

Incivek- telaprevir- Clinical Trials

Incivek- telaprevir- Clinical Trials

Incivek- telaprevir- Clinical Trials

Incivek- telaprevir- Clinical Trials

• “Trial 108” (ADVANCE)- randomized double-blind, parallel-group, placebo controlled trial in treatment-naïve individuals. The trial enrolled 1088 subjects that received Incivek for either 8 or 12 weeks, followed by 48 weeks of Peg-IFN-alpha-2a/RBV treatment.

• “Trial 111” (ILLUMINATE)- Randomized, open-label, trial conducted in 540 treatment-naïve patients. Subjects were given Incivek for 12 weeks followed by either 24 or 48 weeks of Peg-IFN-alpha-2a/RBV treatment.

• “Trial C211” (OPTIMIZE)- Randomized, open-label Phase 3 trial in 740 treatment-naïve subjects. Subjects received 12 weeks of Incivek dosed as either 750mg every 8 hours or 1125mg twice daily. After Incivek was completed, patients received Peg-IFN-alpha-2a/RBV treatment. This trial was to compare dosage forms (2x/day vs. 3x/day).

• “TrialC216” (Realize)- Randomized, double-blind, placebo-controlled trial conducted in 662 subjects that had been previously treated for HCV but were either poor or null-responders.

Source: Incivek PI (upsi_telaprevir.pdf)

Incivek- telaprevir- Clinical Trials

• According to Clinicaltrials.gov, there are 27 additional trials planned for Incivek including:– Patients receiving Paroxetine– Anemic Patients– Patients who had received liver transplants– Patients with Chronic HCV– Incivek therapy with the addition of vitamin D

Source: Clinicaltrials.gov

Victrelis- boceprevir- Patient Site

Victrelis- boceprevir- HCP Site

Victrelis- boceprevir- Indications

Source: Victrelis_pi.pdf

Victrelis- boceprevir- HCP- Dosing

Victrelis- boceprevir- PI- Dosing

4 tablets x 3 doses/day= 12 tablets/day

Source: Victrelis_pi.pdf

Victrelis- boceprevir- financial support

Victrelis- boceprevir- patient support

Victrelis- boceprevir- patient support

Victrelis- boceprevir- HCP Support

Victrelis- boceprevir- HCP- Formulary Coverage

Victrelis: Lead-in phase

Victrelis- boveprevir- HCP Site-Clinical Trials-

Victrelis- boveprevir- HCP Site-Clinical Trials-

Victrelis- boveprevir- HCP Site-Clinical Trials-

Victrelis- boveprevir- HCP Site-Clinical Trials-

Victrelis- boveprevir- HCP Site-Clinical Trials-

Victrelis- boveprevir- HCP Site-Clinical Trials-

Victrelis- boveprevir- HCP Site-Clinical Trials-

Victrelis- boveprevir- HCP Site-Clinical Trials-

Victrelis- boveprevir- HCP Site-Clinical Trials-

Victrelis- boceprevir- HCP Site-Clinical Trials-

Victrelis- boceprevir- Clinical Trials:

• SPRINT-2 Trial (Approximately 1100 treatment naïve patients)• RESPOND-2 Trial (Approx. 400 subjects that had failed with previous

peginterferon/ribivarin therapy)

Each trial was a randomized, double-blind, placebo-controlled study comparing Victrellis 800mg 3x daily combined with PegIntron and Rebetol with standard PegIntron /Rebetol therapy. Each trial contained three arms:

– PegIntron and Rebetol for 48 weeks– PegIntron and Rebetol for 4 weeks followed by Victrelis 800mg 3x/daily + PegIntron and

Rebetol for 24 weeks– PegIntron and Rebetol for 4 weeks followed by Victrelis 800mg 3x/daily +PegIntron and

Rebetol for 48 weeks

Source: Victrelis_pi.pdf

• According to Clinicaltrials.gov, there are 26 additional trials planned for Victrelis including:– Patients that received liver transplants– Patients who had received liver transplants– Patients with Chronic HCV– Patients of various ethnic groups, including

Hispanic and Asian Populations

Source: Clinicaltrials.gov

Victrelis- boceprevir- Clinical Trials:

HCV Triple Cocktail CostsDrug Cost Unit

Victrelis $6471 336/capsules 28 Days

Incivek $4164 30/pack 10 days

Ribavirin $32 30/pack 15 days

Pegasys $3050 4/pack 4 weeks

Total cost of a 48-week course of treatment can run $65,000- $80,000

Source: Goodrx.com

Protease Inhibitor US Promotional spending (2012)

Drug Mfg. US DTC Media(000’s)

US Journal Media (000’s)

Victrelis Merck $0.00 $640.6

Incivek Vertex $7805.3 $1605.6

mmm-online, June 2013

Incivek Sales Data- Waiting for the Next Big Thing

Drugs.com

HCV Opportunities for growth

• Estimated that the number of patients being “warehoused” for new treatments is causing the drop in sales of current courses of therapy

• Expanded testing guidelines for HCV could cause also raise the number of patients seeking treatment.

• The population receiving treatment to rise from 85,000 to over 150,000

• New treatments are expected to cost 80-100k for a course of treatment

Drawbacks with Current HCV Treatment

• Limited effectiveness:– PEG-Interferon/Ribavirin combo aren’t completely

effective– “Triple Therapies” may be more effective, but the

course of treatment is long and expensive

• The need for weekly injections of PEG-2-Interferon causes a treatment compliance risk.

Buying the Pipeline…

• Many of the next-generation HCV drugs have come through acquisitions rather than in-house development– Gilead purchased Pharmasset for $11 billion– BMS acquired Inhibitex for $2.5 billion– Vertex purchase Virochem for $275 million and

licensed Alios compound for $775 million– Abbot/Abbvie licensed a compound from Enata

for $310 million

Coming Soon….• AbbVie: All oral-combo drug achieved a 99% cure rate in

treatment-naïve responders with genotype 1 HCV after 12 weeks

• BMS: All-oral regimen, including daclatasvir, asunaprevir, and BMS-791325 cured 94% of patients after 12 weeks in phase 2 studies, recently filed in Japan

• J&J: simeprevir 80% cure rate after 24 weeks in genotype 1 patients, NDA filed

• Merck: Combination of MK-5172 and MK-8742 designated “Breakthrough Therapy” by the FDA after presentation of phase 2 data

Gilead: sofosbuvir• Unanimously recommended by FDA advisory panel in

conjunction with ribavirin for genotype 2 & 3 HCV• Treatment time: 12 weeks for genotype 2, 24 weeks

for genotype 3• Expected to be filed for all remaining genotypes of HCV• A two-drug combination of sofosbuvir and ledipasvir

cured 97% of patients after 12 weeks, expected to be launched in 2015

• Expected to eventually be filed for all genotypes of HCVsofosbuvir sales expected to reach annual sales of $4.3- $7 billion

Conclusions

• The HCV market is large and so are the opportunities

• Current protease inhibitors are more effective than previous therapies

• New drug products coming to market will offer increased performance, shorter treatment time, and fewer side effects, but at a significant cost to payers

References• http://www.slideshare.net/jamesweiss18/hepatitis-c-virus-infection-therapeutic-class-report-overview

• http://www.drugtrendreport.com/commercial/specialty-forecast-by-therapy-class

• http://www.mmm-online.com/therapeutic-focus-2013-infectious-diseases/printarticle/293793/

• http://www.drugtrendreport.com/commercial/specialty-forecast-by-therapy-class

• http://www.cdc.gov/hepatitis/hcv/hcvfaq.html

• www.who.int/mediacentre/factsheets/fs164/en/

• http://www.cdc.gov/hepatitis/hcv/hcvfaq.html

• http://www.forbes.com/sites/henrymiller/2013/06/19/a-public-health-and-healthcare-spending-time-bomb-hepatitis-c/

• http://www.fool.com/investing/general/2013/10/23/the-race-is-on-for-the-next-big-hepatitis-c-therap.aspx?source=isesitlnk0000001&mrr=0.20

References• http://www.medscape.com/viewarticle/813197

• http://www.fool.com/investing/general/2013/10/23/the-race-is-on-for-the-next-big-hepatitis-c-therap.aspx

• http://Incivek.com

• http://Victrelis.com

• http://Pegasys.com

• http://www.mercknewsroom.com/news-release/research-and-development-news/merck-receives-breakthrough-therapy-designation-mk-5172mk

• http://www.nytimes.com/2013/11/05/health/hepatitis-c-a-silent-killer-meets-its-match.html?_r=0